1) Field of the Invention
This invention relates to oral antibacterial compositions of penem or carbapenem antibiotics (hereinafter called "penems") with improved gastrointestinal absorption and also to a method for the improvement of gastrointestinal absorption of penems. More specifically, the present invention is concerned with oral antibacterial compositions with improved gastrointestinal absorption of penems and a method for the improvement of gastrointestinal absorption of penems, said compositions and method making use of a substance such as an inhibitor for the dipeptidase localized on/in epithelial cells of the small intestine.
2) Description of the Related Art
Active development of penems is now under way as new generation antibiotics succeeding penicillin and cephalosporin for their broad antibacterial spectrum and high levels of antibacterial activities.
However, actually the effective administration route of carbapenem antibiotics is only intravenous injection, because the carbapenem compounds are practically unabsorbable through the digestive tract.
On the other hand, it has been reported with respect to penem antibiotics that--paying attention to the fact that the kidney is a primary site of metabolism for penem antibiotics--penem antibiotics were administered in combination with a chemical substance capable of selectively inhibiting the enzyme, the .beta.-lactam hydrolase, dipeptidase (E.C.3.4.13.11), localized in the kidney (hereinafter called "the renal dipeptidase inhibitor") (U.S. Pat. No. 4539208). As a method for using a renal dipeptidase inhibitor in combination with penem antibiotics, this U.S. patent discloses that the penem antibiotics and the renal dipeptidase inhibitor can be administered either in the form of a pharmaceutical composition containing these two compounds or be separately administered orally, intramuscularly or intravenously. The U.S. patent contains examples of the combined use, in which penems were administered orally. The method and dosage of the administration of the renal dipeptidase inhibitor, the resulting penem concentrations in plasma, etc. are, however, not satisfactory. Needless to say, the above patent does not suggest any improvement in gastrointestinal absorption.
Under the present circumstances as described above, it is very important for the expansion of the application field of the penems to find out a method to improve their gastrointestinal absorption so that sufficient therapeutic effects can be brought about by their oral administration. There is, therefore, an outstanding demand for the development of such an invention.